Research ArticleAIDS/HIV

MHC Heterozygote Advantage in Simian Immunodeficiency Virus–Infected Mauritian Cynomolgus Macaques

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Science Translational Medicine  10 Mar 2010:
Vol. 2, Issue 22, pp. 22ra18
DOI: 10.1126/scitranslmed.3000524

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Abstract

The importance of a broad CD8 T lymphocyte (CD8-TL) immune response to HIV is unknown. Ex vivo measurements of immunological activity directed at a limited number of defined epitopes provide an incomplete portrait of the actual immune response. We examined viral loads in simian immunodeficiency virus (SIV)–infected major histocompatibility complex (MHC)–homozygous and MHC-heterozygous Mauritian cynomolgus macaques. Chronic viremia in MHC-homozygous macaques was 80 times that in MHC-heterozygous macaques. Virus from MHC-homozygous macaques accumulated 11 to 14 variants, consistent with escape from CD8-TL responses after 1 year of SIV infection. The pattern of mutations detected in MHC-heterozygous macaques suggests that their epitope-specific CD8-TL responses are a composite of those present in their MHC-homozygous counterparts. These results provide the clearest example of MHC heterozygote advantage among individuals infected with the same immunodeficiency virus strain, suggesting that broad recognition of multiple CD8-TL epitopes should be a key feature of HIV vaccines.

Footnotes

  • Citation: S. L. O'Connor, J. J. Lhost, E. A. Becker, A. M. Detmer, R. C. Johnson, C. E. MacNair, R. W. Wiseman, J. A. Karl, J. M. Greene, B. J. Burwitz, B. N. Bimber, S. M. Lank, J. J. Tuscher, E. T. Mee, N. J. Rose, R. C. Desrosiers, A. L. Hughes, T. C. Friedrich, M. Carrington, D. H. O'Connor, MHC heterozygote advantage in smian immunodeficiency virus–infected mauritian cynomolgus macaques. Sci. Transl. Med. 2, 22ra18 (2010).

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